This project will begin a re-examination of the human psychobiology of the tryptamine hallucinogen of abuse, N,N-dimethyltryptamine (DMT). Hallucinogens continue being abused, particularly by young adults. Lack of human psychopharmacological studies prevent relevant interfaces from being made with animal neuropharmacological data. Recent developments in serotonin receptor physiology provide a context within which such human studies may proceed. Specific aims of this one-year grant are: 1) development of a sensitive, specific and reliable gc-ms assay for DMT; 2) recruitment and assessment of a group of well-functioning experienced hallucinogen users for this study; 3) development and validation of a DMT rating scale; and 4)initiation of dose-response studies of the neuroendocrine and psychological effects of DMT. This normative data will provide the foundation for subsequent studies with relevance to drug abuse; e.g. investigating the effects of specific serotonergic subtype antagonists on the psychoneuroendocrine effects of DMT, and attempting to develop tolerance to the acute effects of DMT.